The present invention generally relates to implantable prostheses and to methods for making and treating same to substantially prevent cracking or surface fissuring as well as to provide a nonthrombogenic surface for blood contacting surfaces. More specifically, prostheses made from aromatic polymers such as polyurethane and the like, are treated by sulfonating the aromatic rings of the polymer, the polymeric surface being one that will crack when subjected to subcutaneous implantation for substantial time periods if it is not sulfonated. Additionally, synthetic vascular grafts made from aromatic polymers will experience occlusion of the graft lumen by blood clots, or thrombus, if the polymer is not sulfonated. The sulfonation of such aromatic polymers involves a surface modification of the polymer which is accomplished by the addition of at least one sulfate group (--SO.sub.3 H) to the aromatic rings of the polymer.
Several biocompatible materials which are quite suitable for use in making implantable medical devices which may be broadly characterized as implantable prostheses exhibit properties which are sought after in such devices. Such properties may include biocompatibility, extrudability, moldability, good fiber forming properties, tensile strength, elasticity, durability, and the like. However, some of these otherwise desirable materials exhibit serious deficiencies when implanted subcutaneously. Such deficiencies include the development of cracks or fissures which, for prostheses comprised of relatively thin strands or members, cause a reduction in the overall strength of the prostheses because of the complete severance of a number of the thin strands or members. Often, surface fissuring or cracking occurs after substantial exposure to body fluids such as are encountered during in vivo implantation and use. Substantial periods of use may be on the order of one month or more or less. Many implantable prostheses are intended to be permanent in nature and should not develop any substantial cracking during years of implantation.
In addition to fissuring or cracking, it is well known that a significant mode of failure of small caliber (less than 7 millimeters in diameter) synthetic vascular grafts is due to the total occlusion of the graft lumen, or blood contacting surface, by blood clots, or thrombus formation. Since many implanted prostheses are intended to be permanent, it is desirable to provide a nonthrombogenic surface for blood contacting prostheses.
Several theories have been promulgated in attempting to define the cause of cracking as well as thrombus formation. Proposed mechanisms to explain the cracking phenomenon include oxidative degradation, hydrolytic instability, enzymatic destruction, mechanical failure, immunochemical mechanisms, and inhibition of lipids. Thrombus formation is believed to occur because of the relative ease with which the anionic platelets adhere to the electrically neutral hydrophobic surface of the graft lumen. The hydrophobic nature of the graft lumen prevents rapid hydration of the lumen thereby maximizing the material blood interface and foreign body reaction.
Prior attempts to control surface fissuring or cracking upon implantation include incorporating antioxidants within the biocompatible polymer and subsequently annealing the biocompatible polymer under various conditions, typically including attempting to remove stresses within the polymer by applications of various heating and cooling conditions. Attempts such as these have been largely unsuccessful. It is known in the art that the treatment of certain polymers with certain sulfur containing materials greatly increases or enhances the nonthrombogenicity of the polymer material. In particular, it is known that sulfonated polystyrene demonstrates antithrombogenic activity which is directly related to the surface density of sulfonate groups. However, these known effects are generally accomplished by sulfonation in a manner other than that which is disclosed herein.
Regarding both cracking and nonthrombogenicity, a particular need is evident when attempting to form prostheses with procedures including the extrusion or spinning of polymer fibers, as are involved in winding fiber-forming polymers into porous vascular grafts, such as described in U.S. Pat. No. 4,475,972, the subject matter thereof being incorporated by reference herein. Such vascular grafts include a plurality of strands that are of a somewhat fine diameter such that when cracking occurs after implantation, the cracking is manifested in the form of complete severance of various strands of the vascular graft. Such strand severance cannot be tolerated to any substantial degree when the purpose behind implantation is to provide a fairly permanent graft implant whereby the vascular graft remains viable for a number of years. Likewise, thrombogenicity will often manifest itself in small caliber vascular grafts (less than 7 millimeters in diameter) in the form of total occlusion of the graft lumen. As discussed above in terms of strand breakage and cracking, vascular graft occlusion cannot be tolerated if such grafts are to remain viable for indefinite periods of time.
Numerous vascular graft structures made from spun fibers appear to perform very well insofar as their ability to withstand physical stress conditions which approximate those experienced during and after implantation, including stresses imparted by sutures and the like. For example, certain aromatic polyurethane spun grafts when subjected to constant stress under in vitro conditions, such as in saline solution at body temperature, do not demonstrate the cracking that is evident when substantially the same polyurethane spun graft is subjected to in vivo conditions. Accordingly, while many materials, such as polyurethane, polyester terephthalate, polystyrene, polysulfone and the like, may appear to provide superior medical devices or prostheses when subjected to stress under in vitro conditions, these materials are found to be unsatisfactory when subjected to substantially the same types of stresses but under in vivo conditions.
There is accordingly a need for a treatment which will impart crack preventive properties to aromatic polymers that experience surface fissuring under in vivo conditions as well as imparting antithrombogenic properties to the blood contacting surfaces of such polymers which make up synthetic vascular grafts. Both properties, anticracking and antithrombogenicity, must be available to the treated vascular grafts or prostheses so that cracking and thrombus formation can be successfully avoided after implantation for a period of months or years. Exemplary medical devices or prostheses for which such a treatment would be medically advantageous include vascular grafts, introacular lens loops or haptics, pacemaker lead insulators, permanent sutures, diaphragms for artificial hearts, prosthetic heart valves, and the like.
Objectives of the type mentioned above are met by the present invention which achieves a successful treatment of biocompatible aromatic polymers including polyurethane, polyester terephthalate, polystyrene, polysulfone, aromatic silicone rubbers, and the like so that these treated polymers will not exhibit surface cracking or fissuring under in vivo conditions and to the extent that these treated polymers will exhibit antithrombogenic properties when used as blood contacting surfaces. The invention involves treating the aromatic polymers with a sulfonating agent. Such sulfonating agents include sulfur trioxide vapor and concentrated or fuming sulfuric acid. Most preferably, the sulfonating agent is in the form of an adduct of sulfur trioxide and a primary alcohol. Treatment of a prosthesis with the sulfonating agent can be carried out by a procedure as straight forward as dipping the prosthesis into the sulfonating agent or, in the case of sulfur trioxide vapor, by directly exposing the prosthesis to the sulfur trioxide vapor. It should be noted that the use of sulfur trioxide vapor or concentrated or fuming sulfuric acid is not the preferred treatment for sulfonating fine porous networks, such as filamentous spun polyurethane grafts, because such porous networks generally cannot withstand the heats of reaction from these concentrated sulfonating agents which tend to melt or distort the porous network before the sulfonation reaction is complete. For this reason, a more mild reaction is preferred, such as the reaction between a aromatic polymer and an adduct made from a primary alcohol and sulfur trioxide. Following sulfonation, steps are taken to neutralize residual acid and ionize the resultant sulfate moiety such as by immersing the prostheses in a basic solution containing sodium carbonate or the like. Sulfonation of the polymer can be confirmed by staining the prostheses with a sulfate sensitive dye such as methylene blue.
It is accordingly an object of this invention to provide an improved implanted device, method of its production, and treatment to prevent both cracking and thrombus formation.
Another object of the present invention is to provide an improved vascular graft made from spun fibers and exhibiting an exceptional ability to prevent crack formation, strand severance, and occlusion due to thrombus formation after subcutaneous implantation for substantial periods of time such as those experienced in generally permanent implantation procedures.
Another object of the present invention is to provide an improved production method, treatment method and treated product that imparts the properties of in vivo crack prevention and nonthrombogenicity to biocompatible polymeric materials that exhibit desirable medical properties but otherwise experience cracking and thrombogenicity in in vivo applications.
These and other objects, features and advantages will be clearly understood through a consideration of the following detailed description.